An Efficacy and Safety Study of Enzalutamide Plus Androgen Deprivation Therapy (ADT) Versus Placebo Plus ADT in Chinese Patients With Metastatic Hormone Sensitive Prostate Cancer (mHSPC): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Efficacy and Safety Study of Enzalutamide Plus Androgen Deprivation Therapy (ADT) Versus Placebo Plus ADT in Chinese Patients With Metastatic Hormone Sensitive Prostate Cancer (mHSPC) (NCT04076059), a randomized phase 3 study. The primary outcome is Time to Prostrate Specific Antigen (PSA) Progression.

2. Clinical Question

The clinical question is about the timing of a defined laboratory-based progression event, not about every aspect of disease course or patient experience. The registry reports a hazard ratio for the comparison and a median time for the placebo-plus-ADT group. It does not report a median for the enzalutamide-plus-ADT group. Accordingly, the posted primary result can be described using the reported relative time-to-event analysis, but the registry does not provide a pair of medians for direct comparison.

The study also listed outcomes concerning radiographic progression, symptomatic skeletal events, castration resistance, PSA response, initiation of new antineoplastic therapy, undetectable PSA, and objective response. These are related but distinct questions. Their presence in the registry does not make them interchangeable with the primary PSA-progression outcome, and estimates for some listed outcomes are not reported in the registry record.

3. Trial Design

The registry describes China ARCHES as a multicenter, phase 3, randomized, double-blind, placebo-controlled study with a parallel design and quadruple masking. It enrolled 180 participants. The study compared enzalutamide plus ADT with placebo plus ADT in Chinese patients with metastatic hormone-sensitive prostate cancer. The registry lists a start date of 2019-09-11 and a primary completion date of 2022-11-18; the current status is active, not recruiting.

The double-blind phase had two treatment groups. Participants assigned to enzalutamide received capsules orally once daily if tolerable, alongside ADT. Participants assigned to placebo received matching capsules orally once daily, alongside ADT. The descriptions state that study treatment and ADT continued until radiographic disease progression was documented or another investigational agent or new prostate cancer therapy was started. The full treatment description is not reported in the registry record.

The study also had an open-label phase. Participants who had received placebo and remained on study treatment until confirmed radiographic progression received enzalutamide while continuing ADT. The registry specifies that ADT could be bilateral orchiectomy or an LHRH agonist or antagonist. The posted primary comparison is between the double-blind groups; it should not be read as a randomized comparison of the later open-label treatment phase.

Although the record identifies randomization and masking, the randomization procedure, allocation ratio as a protocol feature, concealment procedures, and masking roles in detail are not reported in the registry record. The record also does not report the trial's original sample-size justification or the detailed statistical analysis plan. Those details should not be inferred from the posted enrollment or outcome estimates.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: Participants who met all inclusion criteria and none of the exclusion criteria were enrolled in the study. Randomization was stratified by volume of disease (low versus high) and prior docetaxel therapy for prostate cancer (no prior docetaxel, prior docetaxel).

Double Blind Phase

Reasons for not completing this period:

Open Label Phase

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: ITT Population

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: The Intent-to-Treat (ITT) population included all participants who were randomized in the study.

6. Primary Endpoint

The registry lists the primary outcome as Time to Prostrate Specific Antigen (PSA) Progression, measured over From the date of randomization to the first observation of PSA progression (up to 38 months).

The primary endpoint is time to PSA progression, measured from randomization to the first observation meeting the registry's definition of PSA progression. The definition requires a rise of at least 25% and an absolute increase of at least 2 microgram/liter (2 nanogram/milliliter) above the nadir, meaning the lowest PSA value observed after baseline or at baseline. The increase had to be confirmed by a second consecutive value at least 3 weeks later. The stated timeframe is up to 38 months.

This endpoint captures when a specified PSA change is observed and confirmed. It is therefore a time-to-event measure: participants may experience the event at different times, and some may not have a recorded event during the observation period. As a general statistical point, time-to-event methods can use information about event timing while accounting for participants whose event time is not observed during follow-up, subject to the analysis and censoring rules. The registry identifies Kaplan-Meier estimates for the time-to-event analysis but does not report the censoring rules in detail.

PSA progression is one way to characterize disease progression in the study; it is not the same endpoint as radiographic progression, symptoms, or survival. The registry reports a median and 95% confidence interval for the placebo-plus-ADT group, but the median for the enzalutamide-plus-ADT group is not reported in the registry record. The primary comparison is therefore most directly described by its reported hazard ratio and confidence interval, rather than by comparing two reported median times.

7. Results Posted in the Registry

• Enzalutamide Plus Androgen Deprivation Therapy (ADT) (Double Blind Phase) vs Placebo Plus ADT (Double Blind Phase): hazard ratio 0.13 (95% CI 0.08–0.22), reported p < 0.001 (as reported in the registry).

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Radiographic Progression-Free Survival (rPFS)

• Endpoint type: Time to event: compared as a hazard ratio.
• Test: Hazard ratio as reported by the sponsor (Log Rank); it was not recalculated.
• Result:
  • Enzalutamide Plus Androgen Deprivation Therapy (ADT) (Double Blind Phase) vs Placebo Plus ADT (Double Blind Phase): hazard ratio 0.33 (95% CI 0.20–0.56), reported p < 0.001 (as reported in the registry).
• Interpretation:
  • The 95% confidence interval excludes no difference (a ratio of 1), so the hazard of the event is statistically lower for Enzalutamide Plus Androgen Deprivation Therapy (ADT) (Double Blind Phase) vs Placebo Plus ADT (Double Blind Phase) than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Time to First Symptomatic Skeletal Event (SSE)

• Endpoint type: Time to event: compared as a hazard ratio.
• Test: Hazard ratio as reported by the sponsor (Log Rank); it was not recalculated.
• Result:
  • Enzalutamide Plus Androgen Deprivation Therapy (ADT) (Double Blind Phase) vs Placebo Plus ADT (Double Blind Phase): hazard ratio 0.79 (95% CI 0.21–3.00), reported p = 0.728 (as reported in the registry).
• Interpretation:
  • The 95% confidence interval includes no difference (a ratio of 1), so these data do not show a statistically significant difference between Enzalutamide Plus Androgen Deprivation Therapy (ADT) (Double Blind Phase) vs Placebo Plus ADT (Double Blind Phase) and the control. The interval gives the range of effects that remain compatible with the data.

Time to Castration Resistance

• Endpoint type: Time to event: compared as a hazard ratio.
• Test: Hazard ratio as reported by the sponsor (Log Rank); it was not recalculated.
• Result:
  • Enzalutamide Plus Androgen Deprivation Therapy (ADT) (Double Blind Phase) vs Placebo Plus ADT (Double Blind Phase): hazard ratio 0.17 (95% CI 0.11–0.28), reported p < 0.001 (as reported in the registry).
• Interpretation:
  • The 95% confidence interval excludes no difference (a ratio of 1), so the hazard of the event is statistically lower for Enzalutamide Plus Androgen Deprivation Therapy (ADT) (Double Blind Phase) vs Placebo Plus ADT (Double Blind Phase) than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes with posted time-to-event comparisons do not all tell the same statistical story. Radiographic progression-free survival and time to castration resistance have reported hazard ratios below the null, with confidence intervals that do not cross it and p-values of < 0.001. The comparison for time to first symptomatic skeletal event is less precise: its confidence interval is wide and its p-value is 0.728. This range of results shows why secondary endpoints need to be read separately rather than summarized as a single uniform finding.

These outcomes provide context around the primary PSA-progression result because they address other progression-related events and clinical measures. They are not the same as PSA progression and cannot replace the primary endpoint. Concordant direction for some progression-related outcomes may be informative, but it does not erase the uncertainty in the skeletal-event comparison or establish a conclusion about every secondary outcome.

The registry lists additional secondary outcomes, including PSA response thresholds, undetectable PSA, initiation of new antineoplastic therapy, and objective response. Their results are not reported in the registry record. Their omission from the posted results means that the overall pattern across every listed secondary endpoint cannot be assessed from the record.

As a general statistical principle, interpreting many outcomes creates a multiplicity concern: the more comparisons examined, the greater the chance that some results appear noteworthy by chance if each is considered without adjustment. The record does not report whether multiplicity was controlled, how secondary endpoints were ordered or prioritized, or whether the posted tests were confirmatory or exploratory. Unadjusted secondary results therefore carry less weight than a prespecified primary result and should be viewed as supportive or exploratory rather than as independent proof of the primary finding.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Radiographic Progression-Free Survival (rPFS)
• Time to First Symptomatic Skeletal Event (SSE)
• Time to Castration Resistance
• Percentage of Participants With PSA Response (≥ 50%)
• Percentage of Participants With PSA Response (≥ 90%)
• Time to Initiation of New Antineoplastic Therapy
• Percentage of Participants With Undetectable PSA (< 0.2 ng/mL)
• Objective Response Rate (ORR)

9. Statistical Interpretation

10. Statistical Methods Explained

What does the primary analysis estimate?

The registry states that time to PSA progression was analyzed with Kaplan-Meier estimates and reports a Cox proportional hazards analysis using the log-rank method. In general, Kaplan-Meier estimation describes the event-time pattern over follow-up while allowing for observations that are censored, meaning the event time is not observed during the available follow-up. The registry does not give the detailed censoring rules or explain how particular missing observations were handled.

A hazard ratio compares the event rates between groups over time within a time-to-event model. A value below the null indicates a lower estimated event hazard in the first-named group relative to the comparator, subject to the model and endpoint definition. It is not a ratio of median times and does not directly state the probability that an individual participant will experience the event. The reported primary hazard ratio is 0.130, with a 95% confidence interval of 0.076 to 0.222.

What role do the log-rank test and Cox model play?

As a general explanation, the log-rank test compares the observed timing of events across groups over follow-up. The Cox proportional hazards model expresses the group comparison as a hazard ratio and relies on a proportional-hazards assumption: the relative hazard is treated as stable over time in the model. The registry identifies these methods but does not report whether the assumption was assessed, how it was assessed, or what would have been done if it did not hold. A reported model estimate should therefore be understood as conditional on the chosen analysis framework, not as proof that the framework's assumptions were verified.

The registry's primary analysis is identified as an ITT Population analysis. In general, an intention-to-treat approach analyzes participants according to their randomized group, regardless of later treatment changes, but the registry record does not provide further detail about the exact analysis set or any exclusions. The record also does not report the full statistical analysis plan, including any additional model covariates or sensitivity analyses.

How should the p-value be read?

A p-value describes how compatible the observed data are with a specified null model, under the assumptions of the analysis. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. The primary result has a reported p-value of < 0.001. That is the sponsor-reported test result; it should be read alongside the hazard ratio, confidence interval, endpoint definition, and study limitations rather than on its own.

The 95% confidence interval expresses uncertainty around the estimated hazard ratio under the analysis. In general, a confidence interval is a range of values compatible with the data and method at the stated confidence level. It is not a guarantee that the true value lies in that particular interval. Its width reflects statistical precision, while the point estimate gives the single estimate at the center of the reported analysis. The interval for the primary comparison does not include the null value for a hazard ratio.

Why can the median and hazard ratio tell different things?

A median time is the time by which half of the analyzed group is estimated to have experienced the event, according to the time-to-event estimate. A hazard ratio instead compares event rates across the follow-up period under the Cox model. These summaries answer related but different questions. The registry reports a median of 9.2 months for placebo plus ADT, but not for enzalutamide plus ADT; its primary between-group result is reported as a hazard ratio. It is not appropriate to infer an unreported median from the hazard ratio or the confidence interval.

As a general statistical point, time-to-event outcomes can be affected by how long participants are followed and by censoring. The stated primary timeframe is up to 38 months. The record does not report the distribution of follow-up time, the number of primary events, or detailed censoring information. Those details would help readers assess how much information contributed to the estimates, but they should not be guessed from the point estimate or p-value.

What is and is not a recalculation?

The time-to-event results are presented using the sponsor-reported hazard ratios. The registry record does not supply individual participant data that would permit an independent reanalysis of event times. Accordingly, the primary comparison should be read as the reported analysis, not as a newly calculated estimate from raw data. Planning illustrations based on an observed effect are a different exercise: they explore hypothetical design requirements under stated assumptions and are not a replacement for the trial's own analysis.

The registry does not report the original sample-size justification, a detailed plan for interim analyses, or the procedures for handling all missing data. These unreported design and analysis features limit how fully the reported estimates can be independently evaluated. General statistical explanations of confidence intervals, censoring, and model assumptions describe concepts; they do not fill in those missing trial-specific details.

11. Confidence Intervals and Precision

The primary hazard ratio is 0.130, with a 95% confidence interval from 0.076 to 0.222. The interval is on one side of the null value for a hazard ratio, so the reported estimate is not merely a point estimate close to no group difference. At the same time, the interval spans a range of possible relative hazard values. It conveys uncertainty about the magnitude of the comparison even though the interval does not cross the null.

A confidence interval is a statistical measure of precision under the analysis method, not a range guaranteed to contain the true effect. As a general concept, narrower intervals indicate greater precision than wider intervals, all else equal. Precision depends on the information in the data and on the analysis, and cannot be judged from a p-value alone. The registry does not report the primary event count or detailed follow-up and censoring information, which would add context for understanding how the estimate was informed.

The placebo-plus-ADT median time to PSA progression is 9.2 months, with a 95% confidence interval from 6.54 to 17.48 months. The corresponding median for enzalutamide plus ADT is not reported in the registry record. Thus, the posted record does not allow a direct comparison of the two median estimates or their precision.

For secondary outcomes, precision varies. The confidence interval for time to first symptomatic skeletal event is especially broad, ranging from 0.208 to 2.998, and its p-value is 0.728. This indicates that the estimate is compatible with a wide range of relative hazards. The intervals for radiographic progression-free survival and time to castration resistance are narrower and do not cross the null value, but those secondary findings remain distinct from the primary outcome and should be interpreted in the context of the overall analysis plan, which is not reported in detail.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size illustrations are planning exercises based on the observed effect, not descriptions of the trial's original design. Their stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect defined as a stated fraction of the observed effect. For time-to-event outcomes, the planning values are total event counts, calculated using the Schoenfeld approach. For other outcomes, values are participants per arm. The original design assumptions and sample-size justification are not reported in the registry record.

The 80% power column represents the number of events or participants required, under those planning assumptions, for an analysis to have an 80% chance of detecting the specified effect if that effect were present. The 90% power column describes the corresponding planning target for a 90% chance. These are hypothetical design probabilities, not probabilities that the reported result is correct and not a measure of how likely the trial was to find its observed result.

Rows that plan for a smaller fraction of the observed effect require more information to detect that effect. For a time-to-event outcome, that information is expressed as events; for other outcome types, it is expressed as participants per arm. The values depend on the assumptions used in the illustration, including the size of the effect being targeted and the allocation assumption. They should not be interpreted as a recommended design without considering the research question and other design features.

These calculations are not observed power. Observed power calculated after a study is completed does not add a useful independent description of the result; the estimate, confidence interval, p-value, and available event information are more informative. The planning figures do not reconstruct the choices made when this trial was designed, and they do not establish that the enrolled sample was adequate for every outcome.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

d is the total number of events needed (Schoenfeld's formula) with 1:1 allocation and proportional hazards.

Worked calculation for this trial

1. Hazard ratio HR = 0.130, so ln(HR) = -2.0402.
2. d = 4 × (1.96 + 0.842)² / [ln(0.130)]² = 7.5, rounded up to 8 events in total for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
hr <- 0.13                              # observed hazard ratio
events_needed <- function(power, frac = 1) ceiling(round(4 * (z_a + qnorm(power))^2 / log(hr^frac)^2, 6))   # Schoenfeld, 1:1 allocation
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: events = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(events_needed(0.80, f), big.mark = ","), format(events_needed(0.90, f), big.mark = ",")))

# Simulation: given d total events under proportional hazards, events in the treatment arm are Binomial(d, hr / (1 + hr)).
# The score (log-rank type) statistic is (D1 - d / 2) / sqrt(d / 4).
set.seed(4076059)
d    <- events_needed(0.80)
reps <- 20000
D1 <- rbinom(reps, d, hr / (1 + hr))
z  <- (D1 - d / 2) / sqrt(d / 4)
cat(sprintf("Simulated power with %s events: %.3f (%d replicates)\n", format(d, big.mark = ","), mean(abs(z) > z_a), reps))

Output from running the code

100% of observed effect: events = 8 (80% power), 11 (90% power)
 75% of observed effect: events = 14 (80% power), 18 (90% power)
 50% of observed effect: events = 31 (80% power), 41 (90% power)
Simulated power with 8 events: 0.775 (20000 replicates)

The simulation uses the fact that, with d events in total and proportional hazards, the number of events in the treatment arm is binomial. It is an approximation that conditions on the total number of events, and it should land close to the target power.

14. Analyses Reported by the Sponsor

The posted primary and secondary time-to-event comparisons use the registry's sponsor-reported hazard ratios and accompanying confidence intervals and p-values. For the primary comparison, the reported estimate is 0.130 with a 95% confidence interval of 0.076 to 0.222 and p < 0.001. The record does not provide participant-level data for an independent recalculation of that hazard ratio, so it should not be described as a new estimate recalculated from the posted group summaries.

The displayed planning illustrations are separate from the sponsor's outcome analysis. They use the observed effect as a basis for hypothetical sample-size and event-count scenarios under stated assumptions. They do not reproduce or validate the trial's analysis, and the original sample-size rationale is not reported in the registry record.

No discrepancy is flagged between the reported analysis and the presentation of the result in the registry record. The sponsor's own reported analysis is therefore the relevant source for the hazard-ratio result; the interpretation should retain its reported estimate, confidence interval, and p-value rather than imply an independent statistical refit. The record does not report enough detail to reproduce the analysis from raw data or to evaluate every modeling decision.

15. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary endpoint and lists secondary outcomes, but the multiplicity strategy is not reported in the registry record. It is not reported whether the study adjusted for testing multiple endpoints, used a hierarchical testing sequence, or designated particular secondary analyses as confirmatory. Without that information, the p-values for secondary outcomes should not be interpreted as if they necessarily account for the full set of analyses.

Missing-data and censoring procedures are also not described in detail. For a time-to-event outcome, participants may have an event observed or may have follow-up end without a recorded event. General time-to-event methods can incorporate censored observations, but conclusions depend on the definitions and assumptions used. The registry names Kaplan-Meier estimation and a Cox proportional hazards analysis for the primary endpoint; it does not report the specific censoring rules, reasons for censoring, or sensitivity analyses addressing departures from those assumptions.

The primary analysis population is identified as the ITT Population. The record does not specify how the analysis population was constructed, how missing endpoint measurements were handled, or whether participants were excluded from any analysis. It also does not report the extent of missing data for the primary or secondary outcomes. These omissions limit assessment of whether missingness could have affected the estimates.

The registry reports randomization and quadruple masking, but does not give detailed implementation procedures. The original sample-size rationale, interim-analysis plan, and full statistical analysis plan are not reported in the registry record. These gaps should not be filled by assumptions based on the enrollment or the observed p-values. They mean that the posted outcomes can be described as reported, while some features needed for a complete appraisal of prespecification, multiplicity, and robustness remain unknown.

16. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cerebral infarction (6.7%), atrial fibrillation (4.3%), vertigo positional (4.3%), urinary tract infection (4.3%), spinal compression fracture (4.3%).

The registry reports serious adverse events, other adverse events, and deaths separately for the double-blind groups and for the open-label enzalutamide-plus-ADT phase. In the double-blind phase, serious adverse events affected 42 of 119 participants at risk in the enzalutamide-plus-ADT group and 12 of 59 at risk in the placebo-plus-ADT group. Other adverse events affected 115 of 119 and 54 of 59, respectively. The registry reports 21 deaths in the enzalutamide-plus-ADT group and 12 in the placebo-plus-ADT group.

For the open-label phase, 5 of 23 participants at risk had a serious adverse event, 16 of 23 had another adverse event, and 8 deaths were reported. This phase involved participants who had previously received placebo and then received enzalutamide with ADT after confirmed radiographic progression. It is not a randomized comparison with the double-blind groups.

The most frequently listed serious adverse event terms include cerebral infarction at 6.7%, and atrial fibrillation, positional vertigo, urinary tract infection, spinal compression fracture, and pathological fracture, each at 4.3%. These are registry-reported terms and percentages; the record does not provide enough detail to infer causation, timing, severity distribution, or comparative risk. Serious adverse events, other adverse events, and deaths are distinct measures and should not be combined into a single safety count. Detailed definitions, follow-up by group, and the statistical approach to safety comparisons are not reported in the registry record.

17. What the Result Does, and Does Not, Mean

The primary result describes a lower estimated hazard of PSA progression in the enzalutamide-plus-ADT group than in the placebo-plus-ADT group during the analyzed follow-up. The reported hazard ratio is 0.130, with a 95% confidence interval of 0.076 to 0.222 and p < 0.001. This is evidence about the timing of the registry-defined PSA event in the randomized double-blind comparison. It is not a direct statement about an individual's prognosis or the probability of progression for a particular patient.

The result does not show that PSA progression was prevented, nor does it provide a median time for the enzalutamide-plus-ADT group. The registry reports a placebo-plus-ADT median of 9.2 months, but the corresponding median in the enzalutamide-plus-ADT group is not reported in the registry record. The hazard ratio should not be translated into an unreported absolute difference in months, an individual probability, or a claim about how long any particular participant remained progression-free.

The primary endpoint is PSA-based, while the study also considered radiographic progression, skeletal events, castration resistance, and other outcomes. A result for one endpoint does not settle every other clinical question. Some secondary comparisons have posted estimates and others are not reported in the registry record; the statistical handling of multiple outcomes is also not reported in detail.

The findings apply to the study population and treatment setting described in the registry. The double-blind groups received ADT in both arms, and some participants assigned to placebo could later receive enzalutamide in an open-label phase after confirmed progression. Thus, the primary comparison concerns the randomized double-blind phase, not a comparison of treatment histories across all later follow-up. The registry record alone does not establish effects in populations or settings it does not describe, nor does it replace consideration of the study's unreported design and analysis details.

18. Why This Trial Matters Statistically

This trial illustrates how a randomized, masked comparison can frame a time-to-event question around a clearly defined endpoint. The primary outcome specifies both the PSA change required and the confirmation procedure, while the analysis reports a hazard ratio with a confidence interval and p-value. Together, these elements make it possible to distinguish the estimated direction of the comparison from its uncertainty and from the event definition itself.

It also illustrates why different statistical summaries should not be conflated. A median describes an estimated event time within a group, whereas a hazard ratio summarizes the relative event hazard over follow-up under a model. In this record, a median is reported for the placebo-plus-ADT group but not for the enzalutamide-plus-ADT group, while the between-group comparison is reported as a hazard ratio. Careful interpretation avoids filling in the missing median or treating the hazard ratio as a difference in months.

The secondary outcomes show why outcome-by-outcome interpretation matters. Some reported progression-related comparisons have estimates in the same direction as the primary comparison, while the symptomatic skeletal event estimate is imprecise. The registry also lists secondary outcomes without posted results. A statistical account that acknowledges both the observed estimates and the reporting gaps is more informative than a blanket statement that all outcomes point to one conclusion.

Finally, the record demonstrates the limits of registry-level appraisal. It reports the main comparison and some methods, but not the full analysis plan, detailed missing-data procedures, or multiplicity approach. Statistical significance is only one part of interpreting a trial; endpoint relevance, precision, design, safety reporting, and the availability of prespecified analysis details also matter.

19. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several limitations are specific to the information in this registry record. The enzalutamide-plus-ADT median for the primary endpoint is not reported, so the record does not support a direct comparison of group median times. The primary event count, detailed follow-up distribution, and censoring information are also not reported, limiting assessment of the information underlying the time-to-event estimate.

The study included a later open-label phase in which some participants previously assigned to placebo could receive enzalutamide after confirmed radiographic progression. The primary reported comparison is from the double-blind groups; the registry does not provide a randomized comparison for the open-label phase. The later treatment experience therefore should not be combined with the primary comparison as though it were another randomized contrast.

The registry lists eight secondary outcomes, but posted estimates are available for only some of them. Results for the other listed outcomes are not reported in the registry record. The multiplicity strategy, detailed statistical analysis plan, original sample-size rationale, and interim-analysis plan are also not reported. These gaps make it difficult to determine how the full set of outcomes was prioritized and whether secondary testing was adjusted.

Safety counts are posted for the treatment phases, but the registry record does not provide full detail on event definitions, timing, exposure, or adjusted comparative analyses. The open-label safety group is not randomized against the double-blind groups. Finally, the record describes a study in Chinese patients with metastatic hormone-sensitive prostate cancer; conclusions should not automatically be extended beyond that population and study setting.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: An Efficacy and Safety Study of Enzalutamide Plus Androgen Deprivation Therapy (ADT) Versus Placebo Plus ADT in Chinese Patients With Metastatic Hormone Sensitive Prostate Cancer (mHSPC) — NCT04076059.
• Registry record last updated 2026-10-20; status last verified 2026-10.
• Results first posted 2023-11-18.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

23. Record Summary

The registry describes a randomized, phase 3, multicenter, double-blind, placebo-controlled parallel study of enzalutamide plus ADT versus placebo plus ADT in Chinese patients with metastatic hormone-sensitive prostate cancer. Enrollment was 180, and the primary endpoint was time to PSA progression in the ITT Population.

The posted primary analysis reports a hazard ratio of 0.130, with a 95% confidence interval of 0.076 to 0.222 and p < 0.001. A median time to PSA progression of 9.2 months is reported for placebo plus ADT; the median for enzalutamide plus ADT is not reported in the registry record. Some secondary time-to-event comparisons are posted, while results for other listed secondary outcomes are not reported.

The record identifies Kaplan-Meier estimation and a log-rank/Cox proportional hazards analysis, but does not report the complete statistical plan, multiplicity approach, detailed missing-data procedures, or original sample-size justification. Safety results are listed separately for the double-blind and open-label phases. The study status is active, not recruiting.